The overall goal of this research program is to describe structurally- novel neurotoxins from marine algae and cyanobacteria which can serve as neurochemical probes in mammalian pharmacology and provide new lead compounds for the pharmacotherapy of various human illnesses. The specific aims and methods for this project begin with the screening of a large number of marine algal extracts in a battery of assays which are designed to detect neurotoxic substances. The primary screening will occur at both performance sites and be composed of a complementary mixture of mechanism-based and mechanism-blind assays. The algal extracts derive from a repository at OSU containing more than 1000; in addition, approximately 100 new collections of algae are made yearly by shallow water SCUBA methods and extracted according to standardized protocols. Following initial dereplication efforts, active extracts will be chromatographed and then followed by re-evaluation of the fractions in the appropriate bioassays. Pure and active compounds resulting from the bioassay-driven isolation process will be subjected to structure elucidation utilizing modern NMR techniques in concert with mass spectrometry and other spectroscopic methods. The pharmacological mechanism of action of new neurotoxins will be determined using a battery of receptor binding and other neurochemical assays. The chemical and pharmacological portfolio's of these newly discovered neurotoxins will be shared with the appropriate pharmaceutical companies for potential development in the areas of epilepsy and neurodegenerative disorders, and when possible, new neurotoxins will be made generally available to the biomedical community. Through established collaborations with various industrial partners, and the NOVASCREEN(R) program, development of these neurotoxins as potential therapeutics will occur as appropriate.